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Biomedical subjects

K Mokbel

Publications and source records attributed to K Mokbel.

At least 19 recordsLinked to original sources
PubMed2006

Does mammary ductoscopy have a role in clinical practice?

BACKGROUND: Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualisation of the mammary ductal epithelium using sub-millimetre fiberoptic microendoscopes inserted through the ductal opening onto the nipple surface. These scopes also provide working channels for insufflation, irrigation, ductal lavage, and possible therapeutic intervention. MD can be performed under local anaesthesia in the office setting. The objective of this study is to assess the technical feasibility of mammary ductoscopy, and examine its role in guiding ductal excision surgery and the early diagnosis of malignancy. METHODS: Mammary ductoscopy (MD) was performed using a 1 mm fiberoptic microendoscope (Mastascope TM) in 26 patients (age range: 14-73 years): 13 patients undergoing mastectomy (n = 12) or lumpectomy (n = 1) for ductal carcinoma (including 12 cases of DCIS and one case of infiltrating ductal carcinoma) and 13 patients with pathological nipple discharge (PND) and benign breast imaging and simple discharge cytology. Of the latter group: 10 procedures were performed under local anaesthesia (LA) in the office setting and 3 procedures were carried out under general anaesthesia (GA) to guide duct excision surgery. The ductoscopic appearances in this group were graded between 0 and 5 (D0-D5) according to the degree of suspicion. RESULTS: Intraoperative MD was accomplished in 11 (84.6%) of 13 patients undergoing surgery for DCIS. MD was unsuccessful in 2 cases: one patient (aged 73 years) had sclerosis of the nipple and one patient had preoperative vital blue injection in the subareolar region as part of the sentinel node biopsy thus resulting in inadequate visualisation. Intraductal pathology was visualised in 8 (80%) of the 10 cases undergoing mastectomy but ductoscopic cytology was positive for malignancy in only 2 cases (sensitivity = 16%, specificity = 100%). In the office setting, MD was accomplished in 9 (90%) out of 10 patients with PND and was well tolerated (mean pain score = 3.8 out of 10: range 0-7). Of these 10 patients; MD was inadequate (D0) in one patient due to complete occlusion of lumen by the lesion, showed a papilloma in 3 patients (D3), duct ectasia (D2) in 3 patients, irregular thickening of the lumen suspicious of DCIS (D4) in one patient and non-specific benign findings (D2) in 2 patients. Three women with benign ductoscopy and ductoscopy-assisted cytology were reassured and treated conservatively. The remaining 7 patients had ductoscopy-guided duct excision which revealed DCIS in one, papilloma in 4 and benign breast disease in 2 patients. Adequate cellular yield was obtained in 7 (70%) out of 10 cases (benign cytology). The three patients who had MD under GA during microdochectomy had benign endoscopic appearances and final histology (one papilloma and 2 cases of duct ectasia). CONCLUSION: MD is technically feasible in most patients and has a potential in the early detection of breast cancer. The procedure can be performed safely in the office setting and should be considered in all patients presenting with a single duct PND. MD has the potential to reduce the number of duct excision procedures and minimise the extent of surgical resection. Ductoscopic cytology is not sufficiently sensitive for the diagnosis of malignancy and the development of a biopsy tool that obtains tissue under direct visualisation is required.

Journal Article↗
PubMed2006

Oncological considerations of skin-sparing mastectomy.

AIM: To review evidence concerning the oncological safety of performing skin-sparing mastectomy (SSM) for invasive breast cancer and ductal carcinoma in situ (DCIS). Furthermore, the evidence concerning RT in relation to SSM and the possibility of nipple preservation was considered. METHODS: Literature review facilitated by Medline and PubMed databases. FINDINGS: Despite the lack of randomised controlled trials, SSM has become an accepted procedure in women undergoing mastectomy and immediate reconstruction for early breast cancer. Compared to non-skin-sparing mastectomy (NSSM), SSM seems to be oncologically safe in patients undergoing mastectomy for invasive tumours smaller than 5 cm, multicentric tumours, DCIS or risk-reduction. However, the technique should be avoided in patients with inflammatory breast cancer or in those with extensive tumour involvement of the skin in view of the high risk of local recurrence. SSM with nipple areola complex (NAC) preservation appears to be oncologically safe, provided the tumour is not close to the nipple and a frozen section protocol for the retro-areolar tissue is followed. Although radiotherapy (RT) does not represent a contraindication to SSM, the latter should be used with caution if postoperative RT is likely, since it detracts from the final cosmetic outcome.

Journal Article↗
PubMed2006

The potential role of dynamic thermal analysis in breast cancer detection.

BACKGROUND: It is presently well accepted that the breast exhibits a circadian rhythm reflective of its physiology. There is increasing evidence that rhythms associated with malignant cells proliferation are largely non-circadian. Cancer development appears to generate its own thermal signatures and the complexity of these signatures may be a reflection of its degree of development. The limitations of mammography as a screening modality especially in young women with dense breasts necessitated the development of novel and more effective screening strategies with a high sensitivity and specificity. The aim of this prospective study was to evaluate the feasibility of dynamic thermal analysis (DTA) as a potential breast cancer screening tool. METHODS: 173 women undergoing mammography as part of clinical assessment of their breast symptoms were recruited prior to having a biopsy. Thermal data from the breast surface were collected every five minutes for a period of 48 hours using eight thermal sensors placed on each breast surface [First Warning System (FWS), Lifeline Biotechnologies, Florida, USA]. Thermal data were recorded by microprocessors during the test period and analysed using specially developed statistical software. Temperature points from each contra-lateral sensor are plotted against each other to form a thermal motion picture of a lesion's physiological activity. DTA interpretations [positive (abnormal thermal signature) and negative (normal thermal signature)] were compared with mammography and final histology findings. RESULTS: 118 (68%) of participating patients, were found to have breast cancer on final histology. Mammography was diagnostic of malignancy (M5) in 55 (47%), indeterminate (M3, M4) in 54 (46%) and normal/benign (M1, M2) in 9 (8%) patients. DTA data was available on 160 (92.5%) participants. Using our initial algorithm, DTA was interpreted as positive in 113 patients and negative in 47 patients. Abnormal thermal signatures were found in 76 (72%) out of 105 breast cancer patients and 37 of the 55 benign cases. Then we developed a new algorithm using multiple-layer perception and SoftMax output artificial neural networks (ANN) on a subgroup (n = 38) of recorded files. The sensitivity improved to 76% (16/21) and false positives decreased to 26% (7/27) CONCLUSION: DTA of the breast is a feasible, non invasive approach that seems to be sensitive for the detection of breast cancer. However, the test has a limited specificity that can be improved further using ANN. Prospective multi-centre trials are required to validate this promising modality as an adjunct to screening mammography especially in young women with dense breasts.

Journal Article↗
PubMed2006

The role of aromatase and 17-beta-hydroxysteroid dehydrogenase type 1 mRNA expression in predicting the clinical outcome of human breast cancer.

INTRODUCTION: There is substantial evidence that breast cancer tissue contains all the enzymes responsible for the local biosynthesis of estrogens from circulating precursors. The cytochrome P-450 aromatase enzyme complex is responsible for the conversion of C19 androgens to estrogens and 17-beta-hydroxysteroid dehydrogenase (17-I(2)-HSD) type 1 catalyses the inter-conversion of estrone to the biologically more potent estradiol. The gene encoding for the cytochrome P-450 aromatase is known as CYP19 (15q21.2). It is well established that increased exposure to local estrogens is an important risk factor in the genesis and growth of breast cancer. The aim of this study is to investigate the relationship between CYP19 and 17-beta-HSD type 1A mRNA expression and clinico-pathological parameters of human breast cancer. METHODS: One hundred and twenty seven tumor tissues and 33 normal tissues were analyzed. The levels of transcription of CYP19 and 17-beta-HSD type 1 were determined using real-time quantitative PCR. The mRNA expression was normalized against CK19. Levels of expression were analyzed against tumorâ's stage, grade, nodal status, local relapse, distant metastasis and survival over a 120A months follow up period. In addition, the levels were analyzed against estrogen receptor (ER) and HER1-4 status. RESULTS: Overall, high tumor levels of mRNA expression of CYP19 and 17-beta-HSD type 1 correlated with poor survival (p=0.0105 and p=0.0182, respectively). Increased levels of CYP19 mRNA expression positively correlated with disease progression as levels were significantly higher in samples of patients who had distant metastasis and local recurrence and/or died of breast related causes when compared to those who were disease free for >10 years (p=0.0015). We also observed higher levels of CYP19 mRNA in tumor samples compared to normal breast tissue. However, this reached statistical significance only when comparing grade 1 tumors with normal tissue (p=0.01). There was no correlation between CYP19á mRNA expression and tumor stage, lymph node status and tumor grade. There was however a trend for a positive correlation between CYP19 and ER mRNA expressions (p=0.06). No significant difference in 17-beta-HSD type 1 expression between normal and cancerous tissues was observed. In tumor samples, we observed an increase in levels correlating with tumor's grade. This correlation was statistically significant when we compared grade 1 with grade 2 and grade 1 with grade 3 (p=0.0031 and 0.0251, respectively). CONCLUSION: Our study shows that higher levels of the enzymes responsible for the local biosynthesis of estrogens especially aromatase are associated with a poor clinical outcome in patients with breast cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

Screening mammography in women aged 40-49: is it time to change?

There is little doubt that significant benefits can accrue from carrying out screening mammography of women aged 40-49 in the setting of a highly quality assured service delivery. This will best be achieved using digital mammography to maximise detection rates and trained and high volume reading expert radiologists to apply economic cushions of optimising specificity as well as sensitivity in addition to utilising modern and accurate assessment and tissue sampling techniques that have evolved.

Journal Article↗
PubMed2006

Breast papillomas: current management with a focus on a new diagnostic and therapeutic modality.

Breast papilloma is a term that describes an intraductal papillary configuration of the mammary epithelium on macroscopic or microscopic examination. It includes solitary intraductal papillomas, multiple papillomas, papillomatosis, and juvenile papillomatosis (JP).Recent advances in mammary ductoscopy (MD) have raised new possibilities in the diagnosis and treatment of breast papillomas. This technique represents an important diagnostic adjunct in patients with pathological nipple discharge (PND) by allowing direct visualisation and biopsy of intraductal lesions and guiding duct excision surgery. Treatment of breast papillomas often entails surgical duct excision for symptomatic relief and histopathological examination. Recently, more conservative approach has been adapted. MD-assisted microdochectomy should be considered the procedure of choice for a papilloma-related single duct discharge. Furthermore, there is increasing evidence that MD has the potential to reduce the number of duct excision procedures and minimise the extent of surgical resection. Imaging-guided vacuum-assisted core biopsy can be diagnostic and therapeutic for papillomas seen on mammography and/or ultrasound. Patients with multiple papillomas do have an increased risk of developing cancer and should be kept under annual review with regular mammography (preferably digital mammography) if treated conservatively. Magnetic resonance (MR) can be also used in surveillance in view of its high sensitivity. Because the risk is small, long term and affects both breasts, long-term follow-up is more appropriate than prophylactic mastectomy. Patients who prove to have solitary duct papilloma have insufficient increase in the risk of subsequent malignancy to justify routine follow-up.

Journal Article↗
PubMed2005

Skin and fat necrosis of the breast following methylene blue dye injection for sentinel node biopsy in a patient with breast cancer.

Sentinel lymph node biopsy (SLNB) is a simple technique that uses subdermal or peri-tumoral injection of vital blue dye and/or radioactive isotope to identify the first lymph node(s) draining the primary tumor. It has been shown to accurately predict axillary node status in patients with clinically node negative breast cancer. The SLNB is emerging as a new standard of care in patients with early breast cancer. However, the use of methylene blue (MB) dye can be associated with a number of local complications due to its tissue reactive properties. We report a rare case of skin and fat necrosis followed by a dry gangrene of the skin in a female patient with breast cancer who underwent SLNB localization using peri-tumoral injection of MB dye in another institution. This case and literature review suggest that the use of MB dye for SLNB identification should be avoided and replaced with alternative types of blue dye such as Patent Blue V preferably in conjunction with a radioactive isotope tracer.

Journal Article↗
PubMed2005

hTERT protein expression is independent of clinicopathological parameters and c-Myc protein expression in human breast cancer.

BACKGROUND: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. The hTERT (human telomerase reverse transcriptase) subunit seems to be the rate-limiting determinant of telomerase and knowledge of factors controlling hTERT transcription may be useful in therapeutic strategies. The hTERT promoter contains binding sites for c-Myc and there is some experimental and in vitro evidence that c-Myc may increase hTERT expression. We previously reported no correlation between c-Myc mRNA expression and hTERT mRNA or telomerase activity in human breast cancer. This study aims to examine the correlation between hTERT expression as determined by immunohistochemistry and c-Myc expression, lymph node status, and tumour size and grade in human breast cancer. MATERIALS AND METHODS: The immunohistochemical expression of hTERT and c-Myc was investigated in 38 malignant breast tumours. The expression of hTERT was then correlated with the lymph node status, c-Myc expression and other clinicopathological parameters of the tumours. RESULTS: hTERT expression was positive in 27 (71%) of the 38 tumours. 15 (79%) of 19 node positive tumours were hTERT positive compared with 11 (63%) of 19 node negative tumours. The expression was higher in node positive tumours but this failed to reach statistical significance (p = 0.388). There was no significant association with tumour size, tumour grade or c-Myc expression. However, hTERT expression correlated positively with patients' age (correlation coefficient = 0.415, p = 0.0097). CONCLUSION: hTERT protein expression is independent of lymph node status, tumour size and grade and c-Myc protein expression in human breast cancer.

Journal Article↗
PubMed2005

Is preoperative core biopsy accurate in determining the hormone receptor status in women with invasive breast cancer?

BACKGROUND: The objective of this study was to determine the concordance rate between core needle biopsy (CNB) and surgical excision of invasive breast cancer regarding the oestrogen receptor (ER) and Progesterone receptor (PgR) status as determined by Immunohistochemistry (IHC). METHODS: Hormone receptor status was established using IHC (using quickscore system 0-8) on preoperative CNB and subsequent surgical excision in 93 patients with invasive breast cancer. Results were compared taking into account tumour's size, grade, and patient's age. RESULTS: The ER concordance rate between CNB and surgical excisions was 95%. The PgR concordance rate was 89%. This shows that CNB has a sensitivity of 97% for ER and 95% for PgR. There is a positive correlation of ER and PgR between CNB and surgical excision (p < 0.000001). There was no significant difference in the number of core biopsies between concordant and discordant cases. CONCLUSION: Preoperative core biopsy is highly sensitive for the IHC detection of ER and PgR in invasive breast cancer. The concordance rate is higher for ER than PgR, which could be due to the fact that ER is more homogeneously distributed.

Journal Article↗
PubMed2005

Pneumothorax after a clinical breast fine-needle aspiration of a lump in a patient with Poland's syndrome.

We report the first case in the medical literature of a pneumothorax complicating fine needle aspiration cytology (FNAC) of a breast lump in a woman with a mild form of Poland's syndrome. The pneumothorax was treated conservatively. This is the first case of breast FNA-related pneumothorax seen in our clinical practice. We believe that the absence of pectoral muscles has increased the risk of this complication. We have also diagnosed an incidental screen-detected breast cancer affecting the ipsilateral breast in the same patient. We conclude that caution should be exercised when performing FNAC of breast lesions in patients with Poland's syndrome. The procedure should be preferably performed under image guidance in such patients in order to minimise the risk of this complication.

Journal Article↗
PubMed2005

SYK expression in human breast cancer.

BACKGROUND: Syk (Splenic Tyrosine Kinase) is an intracellular receptor protein kinase involved in cell proliferation, differentiation and phagocytosis. It has been studied in T and B lymphocytes, NK cells and platelets. The strong expression of Syk in mammary gland prompted research into its potential role in mammary carcinogenesis. There have been very few studies about its role in breast cancer with conflicting results. This study aims to investigate the hypothesis that Syk expression is down-regulated in breast cancer compared with ANCT and the association between its expression and clinicopathological parameters. MATERIALS AND METHODS: mRNA was extracted from 48 breast cancer specimens. Relative Syk to ribosomal RNA expression was determined by RT-PCR and Taqman methodology. Mann-Whitney U test was used to examine the association between Syk expression in cancer and ANCT. Spearman's rank correlation test was used to examine the association between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion and clinical outcome. RESULTS: The median for the relative value of Syk expression was 0.17 and 0.18 (range: 0.12 - 0.56 and 0.0 - 1.77) for tumours and ANCT respectively. There was no significant association between Syk expression in cancers and ANCT (p= 0.598) nor between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion or prognosis. CONCLUSION: This study shows that Syk mRNA expression does not seem to vary between breast tumours and ANCT. Furthermore, we observed no significant association between Syk expression and clinicopathological parameters.

Journal Article↗
PubMed2005

The evolving role of the dynamic thermal analysis in the early detection of breast cancer.

It is now recognised that the breast exhibits a circadian rhythm which reflects its physiology. There is increasing evidence that rhythms associated with malignant cells proliferation are largely non-circadian and that a circadian to ultradian shift may be a general correlation to neoplasia.Cancer development appears to generate its own thermal signatures and the complexity of these signatures may be a reflection of its degree of development.The limitations of mammography as a screening modality especially in young women with dense breasts necessitated the development of novel and more effective screening strategies with a high sensitivity and specificity. Dynamic thermal analysis of the breast is a safe, non invasive approach that seems to be sensitive for the early detection of breast cancer.This article focuses on dynamic thermal analysis as an evolving method in breast cancer detection in pre-menopausal women with dense breast tissue. Prospective multi-centre trials are required to validate this promising modality in screening.The issue of false positives require further investigation using molecular genetic markers of malignancy and novel techniques such as mammary ductoscopy.

Editorial↗
PubMed2005

Evidence for a tumour suppressive function of APRG1 in breast cancer.

INTRODUCTION: Deletion mapping studies have shown that genes in the region 3p21.3 are often deleted in epithelial malignancies. Although the regions deleted differ between individual cancers there appears to be a specificity for the type of malignancy produced. As a result this area of chromosome 3 is thought to contain multiple tumour suppressor genes. The present study concentrates on one gene in that region, APRG1. This gene codes for a protein, which has been implicated in cell membrane interactions. The aim was to determine using quantitative PCR whether the levels of this gene were negatively correlated with clinical outcome in breast cancer. METHODS: One hundred and twenty tumour tissues and 33 normal tissues were analyzed. Levels of transcription of APRG1 were determined using real-time quantitative PCR. APRG1 expression was normalized against CK19. Levels of expression were analyzed against staging, nodal involvement, grade, distant metastasis and survival over a 6 year follow up period. RESULTS: Levels of APRG1 mRNA were lower in malignant tissues. They fell further with increasing stage using the TNM classification This became statistically significant when TNM stages 3 and 4 were compared to TNM 1 (p = 0.0046, p = 0.04, t-test). They were lower in those with positive nodes although this did not reach statistical significance. There was a statistically significant reduction in APRG1 in grade 3 tumours cf. grade 1 (p = 0.0081). APRG1 expression was highly negatively correlated with progressive disease: alive with metastasis (p = 0.0069), local recurrence (p = 0.0055), died of breast cancer (p = 0.11), all progressive disease (p = 0.035). CONCLUSION: This study shows a compelling trend for APRG1 transcription levels to be lower in malignant tissues and lower still in those patients who develop progressive disease. There was also a statistically significant difference in APRG1 levels between grade 3 and grade 1 tumours. These results are highly suggestive of APRG1 acting as a tumour suppressor gene.

Breast Neoplasms↗
PubMed2004

Evidence for the management of mastalgia.

Mastalgia is the commonest breast symptom presenting to general practitioners and breast surgeons alike. To make a full assessment of the cause, all patients require a full history, examination and, sometimes, investigations. Diary cards are often helpful. The commonest cause is cyclical mastalgia. Most women require reassurance only and the pain often settles spontaneously after a few months. For the remainder, simple lifestyle changes should be suggested initially, such as wearing a well-fitted sports bra, weight reduction, regular exercise and a reduction in caffeine intake. Unfortunately, there is a paucity of evidence for the usefulness of these measures. If pain is persistent or severe, a variety of pharmacological agents exist. The most effective with least side effects is a 3-6-month course of low-dose tamoxifen (10mg). Other proven agents include danazol and bromocriptine, but these have a higher side-effect profile and are rarely indicated nowadays. Newer treatments include lisuride maleate and topical non-steroidal anti-inflammatory preparations.

Breast Diseases↗